Oral contraceptives highlight the genotype-specific association between serum phospholipids and activated factor VII.

The present analysis was undertaken to study the effect of oral contraceptive (OC) use on activated factor VII (FVIIa) in subjects characterized by FVII genotypes, with the further aim of evaluating the role of lipids in this pharmacological interaction. In OC users (n=42) and nonusers (n=130) of comparable age, we examined the FVII phenotypic variables (FVII coagulant activity [FVIIc], FVII antigen, and FVIIa), FVII genotypes (the 353R/Q and 5'F7 polymorphisms analyzed in combination; alleles M1/M2 and A1/A2, respectively), and a number of lipid and lipoprotein parameters: serum concentrations of total cholesterol (chol), low density lipoprotein and high density lipoprotein-chol, triglycerides, phospholipids (PhLs), apolipoprotein A1, and lipoprotein(a). PhLs, triglycerides, apolipoprotein A1, chol, FVII antigen, FVIIc, and high density lipoprotein-chol levels were shown to be statistically higher in users than nonusers. FVII levels, particularly those of FVIIa and FVIIc, were much higher in homozygotes for the A1 and M1 alleles (A11 M11), especially in OC users. A strong association was found between PhL and FVIIa: in the multiple regression analysis, women taking OCs who had elevated PhL concentrations also had very high levels of FVIIa, but only if their genotype was A11 M11. These results indicate that the increased FVII levels in OC users depend on the FVII genotype and that high PhL concentrations predict very high levels of FVIIa and FVIIc.

Inhibition of the synthesis of macromolecules by ethanol in regenerating rat liver.

The effects of ethanol on DNA and protein synthesis of regenerating rat liver has been studied. A single dose of ethanol, when given either before, at the time or 1 h after the partial hepatectomy significantly inhibited the accelerated synthesis of ornithine decarboxylase protein which was used as a marker of protein synthesis. Ethanol seemed to inhibit the synthesis of ornithine decarboxylase at transcriptional level of protein synthesis and the inhibition appeared to be directly due to the presence of ethanol molecules. When rats were chronically fed with ethanol-containing liquid diet also the total protein synthesis was inhibited during the two first days of regeneration. In this experiment also the rate of DNA synthesis was greatly inhibited by ethanol treatment. The results show that the ethanol-induced inhibition of the synthesis of tissue macromolecules is ideally demonstrated in regenerating rat liver. Furthermore they suggest that this effect may be of importance in the progression of alcoholic liver injury.